PURPOSE:

Hyperpolarized Carbon (¹³C) MR spectroscopy allows for in vivo measurements of metabolic conversion including ¹³C-pyruvate to lactate, which is upregulated in brain cancer¹. Phosphorus (³¹P) MRS can be used to quantify ATP levels, allowing for complementary monitoring of bioenergetics in tumors². In this work, we constructed a dual tuned ¹³C/³¹P coil for acquiring metabolism and energetics data to study cancer metabolism in a single setting. As a first step towards this goal, we tested the coil on a healthy rat brain.

METHODS:

Experiments were carried out on a 3 T animal MRI scanner (Biospec, Bruker, Billerica MA), and animal experiments were done in accordance to the IACUC. The ¹³C/³¹P coil was constructed such that the inner loop was tuned to 51.65 MHz (³¹P frequency) and the outer loop was tuned to 32.09 MHz (¹³C frequency) and matched to 50 Ohms when loaded with a saline phantom (Fig 1). An LCC trap circuit³, consisting of an inductor and capacitor in parallel with another capacitor, on the ¹³C coil was used to block currents at the ³¹P frequency to decouple the two channels of the multinuclear coil. Tuning and matching were adjusted to obtain input power reflection less than 20 % at the respective center frequency inside the scanner. Either the ¹³C or ³¹P channel was connected to the X-nucleus channel on the scanner, while the other channel was terminated with a 50 Ohm load. Anatomical localization and B0 shimming were carried out using a volume proton (¹H) coil (72 mm diameter, Bruker, MA). A coil file allowing for changing between the ¹H, ¹³C, and ³¹P channels was constructed in ParaVision 6.0.1.

For adjusting center frequency and system reference power for both channels, a spherical phantom (~200uL: 2M 1-¹³C-sodium acetate, 2M diethyl(2-oxopropyl) phosphonate) was positioned at the center of the coil (Fig 1). Diethyl(2-oxopropyl) phosphanate was specifically chosen so that its phosphorus spectrum does not overlap with in vivo spectra. The system reference power for a 90 degree flip angle was calculated by varying the transmit power of a series of single pulse acquisitions. In order to visualize the conversion of pyruvate to its downstream metabolic products in vivo, a bolus of hyperpolarized [1-¹³C] pyruvate (Testbed, Oxford Instruments, Oxfordshire UK) was administered to a healthy rat via tail vein. Slice selective spectroscopic sequences were used to obtain ¹³C (flip angle = 30 degrees, slice thickness = 10 mm, TR = 3s, repetitions = 64, spectral points = 2048, spectral bandwidth = 6421.23 Hz) and ³¹P (flip angle = 60 degrees, slice thickness = 15 mm, TR = 4s, averages = 256, spectral points = 2048, spectral bandwidth = 6421.23 Hz) spectra through the brain during a single scan session. Data were reconstructed in Mnova (MestReNova, 14.1.0).

RESULTS:

The Phosphorus spectrum in the brain showed clear Phosphocreatine and ATP peaks. In addition, inorganic phosphate, phosphomonoesters, and phosphodiesters were also observed (Fig 2). The summed (Fig 3) and first 14 time frames (Fig 4) of the carbon spectra show the downstream metabolic products of ¹³C-pyruvate, namely lactate, alanine, and bicarbonate. Slice positioning for both phosphorus and carbon spectroscopic acquisitions are shown in the sagittal anatomical slice obtained with the proton volume coil (Fig 2 and 3).

DISCUSSION:

A number of dual tuned coil arrays have been constructed to allow for proton imaging for anatomical localization as well as X-nucleus imaging^4,5. This work demonstrates the implementation of a ¹³C/³¹P coil in combination with an existing volume ¹H coil to visualize metabolism, energetics, and anatomy. A nested loop design for the ¹³C/³¹P coil was chosen over a single loop design with two resonances in order to include an LCC trap on the lower frequency coil, which has been shown to improve coil sensitivity³. Future work on the coil includes the addition of cable traps for both channels to minimize common mode currents on the cables, and implementation of a switch to change between the ³¹P and ¹³C channels.

CONCLUSIONS:

Non-invasive visualization of ¹³C labeled pyruvate and its downstream products in conjunction with ³¹P spectroscopy in the rat brain can be achieved using a ¹³C/³¹P coil.

Acknowledgements

This work was supported by NIH Training Grant T32CA151022, American Cancer Society Research Scholar Grant 18-005-01-CCE, NIH grant P41 EB013598 and P41 EB017183. The authors would like to thank Rohan Virgincar for discussions regarding creating multinuclear coil files in ParaVision.